CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells

被引：120

作者：

Giese, Arnaud P. J. ^{[1
]}

Tang, Yi-Quan ^{[2
]}

Sinha, Ghanshyam P. ^{[3
]}

Bowl, Michael R. ^{[4
]}

Goldring, Adam C. ^{[5
]}

Parker, Andrew ^{[4
]}

Freeman, Mary J. ^{[3
]}

Brown, Steve D. M. ^{[4
]}

Riazuddin, Saima ^{[1
]}

Fettiplace, Robert ^{[5
]}

Schafer, William R. ^{[2
]}

Frolenkov, Gregory I. ^{[3
]}

Ahmed, Zubair M. ^{[1
]}

机构：

[1] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA

[2] MRC Lab Mol Biol, Div Neurobiol, Cambridge Biomed Campus, Cambridge CB2 0QH, England

[3] Univ Kentucky, Dept Physiol, Coll Med, Lexington, KY 40536 USA

[4] MRC Harwell Inst, Mammalian Genet Unit, Harwell Campus, Didcot OX11 0RD, Oxon, England

[5] Univ Wisconsin, Sch Med, Dept Neurosci, Madison, WI 53706 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

CHANNEL-LIKE PROTEINS; MAMMALIAN INNER-EAR; BIOCHEMICAL-CHARACTERIZATION; NONSYNDROMIC DEAFNESS; BULLFROGS SACCULUS; FAST ADAPTATION; ACTIN DYNAMICS; MYOSIN-XVA; CALCIUM; STEREOCILIA;

D O I：

10.1038/s41467-017-00061-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inner ear hair cells detect sound through deflection of stereocilia, the microvilli-like projections that are arranged in rows of graded heights. Calcium and integrin-binding protein 2 is essential for hearing and localizes to stereocilia, but its exact function is unknown. Here, we have characterized two mutant mouse lines, one lacking calcium and integrin-binding protein 2 and one carrying a human deafness-related Cib2 mutation, and show that both are deaf and exhibit no mechanotransduction in auditory hair cells, despite the presence of tip links that gate the mechanotransducer channels. In addition, mechanotransducing shorter row stereocilia overgrow in hair cell bundles of both Cib2 mutants. Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia.

引用

页数：13

共 52 条

[1]

Adams A. C, 2006, MAMMALIAN AVIAN TRAN

[2] The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15 [J].

Ahmed, Zubair M. ;

Goodyear, Richard ;

Riazuddin, Saima ;

Lagziel, Ayala ;

Legan, P. Kevin ;

Behra, Martine ;

Burgess, Shawn M. ;

Lilley, Kathryn S. ;

Wilcox, Edward R. ;

Riazuddin, Sheikh ;

Griffith, Andrew J. ;

Frolenkov, Gregory I. ;

Belyantseva, Inna A. ;

Richardson, Guy P. ;

Friedman, Thomas B. .

JOURNAL OF NEUROSCIENCE, 2006, 26 (26) :7022-7034

[3] VOLTAGE DEPENDENCE OF ADAPTATION AND ACTIVE BUNDLE MOVEMENT IN BULLFROG SACCULAR HAIR-CELLS [J].

ASSAD, JA ;

HACOHEN, N ;

COREY, DP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) :2918-2922

[4] Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia [J].

Belyantseva, IA ;

Boger, ET ;

Naz, S ;

Frolenkov, GI ;

Sellers, JR ;

Ahmed, ZM ;

Griffith, AJ ;

Friedman, TB .

NATURE CELL BIOLOGY, 2005, 7 (02) :148-U60

[5] Development and localization of reverse-polarity mechanotransducer channels in cochlear hair cells [J].

Beurg, Maryline ;

Goldring, Adam C. ;

Ricci, Anthony J. ;

Fettiplace, Robert .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (24) :6767-6772

[6] Subunit determination of the conductance of hair-cell mechanotransducer channels [J].

Beurg, Maryline ;

Xiong, Wei ;

Zhao, Bo ;

Mueller, Ulrich ;

Fettiplace, Robert .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (05) :1589-1594

[7] Localization of inner hair cell mechanotransducer channels using high-speed calcium imaging [J].

Beurg, Maryline ;

Fettiplace, Robert ;

Nam, Jong-Hoon ;

Ricci, Anthony J. .

NATURE NEUROSCIENCE, 2009, 12 (05) :553-558

[8] Biochemical characterization and expression analysis of a novel EF-hand Ca2+ binding protein calmyrin2 (Cib2) in brain indicates its function in NMDA receptor mediated Ca2+ signaling [J].

Blazejczyk, Magdalena ;

Sobczak, Adam ;

Debowska, Katarzyna ;

Wisniewska, Marta B. ;

Kirilenko, Aneta ;

Pikula, Slawomir ;

Jaworski, Jacek ;

Kuznicki, Jacel ;

Wojda, Urszula .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2009, 487 (01) :66-78

[9] Hair-bundle movements elicited by transepithelial electrical stimulation of hair cells in the sacculus of the bullfrog [J].

Bozovic, D ;

Hudspeth, AJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (03) :958-963

[10] The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping [J].

Brown, Steve D. M. ;

Moore, Mark W. .

MAMMALIAN GENOME, 2012, 23 (9-10) :632-640

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